Opportunistic Viral infections Flashcards
Which groups of people are most at risk from opportunistic infections?
Immunocompromised
Impaired ability to respond normally to an infection
- Metabolic/ Endocrine:
- Alcohol Abuse
- Diabetes Mellitus
- Uraemia
- Malnutrition
Impaired Barriers to Infection:
- Burns
- Haemodialysis
- IVDU
Pregnancy, Extremes of Age
What virus and genetic lesion causes epidermodysplasia verruciformis?
- EBV/perforin
- HSV/UNC93B
- HPV/EVER1 or EVER2
- HHV8/STIM1
- None of the above
- HPV/ EVER1/EVER2
Name some AIDS defining illnesses
- Candidiasis of the esophagus, bronchi, trachea, or lungs
- Cervical cancer, invasive
- Coccidioidomycosis, disseminated or extrapulmonary
- Cryptococcosis, extrapulmonary
- Cryptosporidiosis, chronic intestinal (greater than one month’s duration)
- Cytomegalovirus disease (other than liver, spleen, or nodes)
- Cytomegalovirus retinitis (with loss of vision)
- Encephalopathy, HIV related
- Herpes simplex: chronic ulcer(s) (more than 1 month in duration); or bronchitis, pneumonitis, or esophagitis
- Histoplasmosis, disseminated or extrapulmonary
- Isosporiasis, chronic intestinal (more than 1 month in duration)
- Kaposi sarcoma
- Lymphoma, Burkitt’s (or equivalent term)
- Lymphoma, immunoblastic (or equivalent term)
- Lymphoma, primary, of brain
- Mycobacterium avium complex or M kansasii, disseminated or extrapulmonary
- Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
- Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
- Pneumocystis jiroveci pneumonia
- Pneumonia, recurrent
- Progressive multifocal leukoencephalopathy
- Salmonella septicemia, recurrent
- Toxoplasmosis of brain
- Wasting syndrome due to HIV
What are the major classes of immunosuppressive agents?
- Glucocortisteroids or Steroids
- Calcineurin inhibitors (T cell function)
- Cyclosporine
- Tacrolimus
- Antiproliferative agents
- Azathioprine
- Mycophenolate mofetil (MMF) or Mycophenolic Acid (MPA)
- Sirolimus
- Antibodies:
- Depleting
- Non-depleting
- Anti-CD25 receptor antibodies
- Costimulation blockers - belatacept
- Co-stimulation blockers
Which one of the following has the highest relative risk of opportunistic infections e.g. herpes reactivation?
- Cytotoxic chemotherapy
- Advanced HIV infection
- Steroids use
- Allogenic stem cell transplant
- Solid organ transplant
- Allogenic stem cells transplant
Highest relative risk
Allogeneic stem cell transplant
Advanced HIV infection (CD4 dep)
Solid organ transplant
Various monoclonal antibody therapies
Cytotoxic chemotherapy
DMARDs and steroids
Lowest relative risk
Describe how opportunistic viral infections need to be treated and the risks involved
- Opportunistic viral infections are often more difficult to treat
- Often requires
- Early treatment
- higher dose
- longer course
- sometimes drug combinations
- Increased risk of antiviral drug resistance
- What viruses are part of the herpes group?
- What types of virus are the herpes group?
- Can they cause latent infection?
1.
- Herpes simplex virus (HSV) 1 & 2
- Varicella zoster virus (VZV)
- Cytomegalovirus (CMV)
- HHV6 : Human herpes virus 6
- Epstein Barr Virus (EBV)
- HHV-8
- DNA viruses
- Yes they can cause latent infection
- Only a small subset of genes are expressed
- Reactivation can occur leading to the expression of viral genes and production of progeny virus
- Leads to destruction of the host cells
A 45-year-old lady undergoes an Stem cell transplant. Which of these viral infections is most likely to develop in the first 10-20 days post-transplant?
- CMV
- HSV
- VZV
- HHV7
- HHV6
- HSV
VZV, EBV and CMV develop months later
- What does HSV commonly cause?
- What are the serious complications of HSV?
- What is the treatment?
- Common:
- Cold sores, stomatitis, mouth ulcers
- Recurrent genital disease (HIV and adult transplant)
- Serious complications
- Cutaneous dissemination
- Oesophagitis
- Hepatitis
- Viraemia
- Treatment
- Aciclovir or valaciclovir
- Foscarnet
- (Ganciclovir sensitive also)
- VZV in the immunocompromised, what are the serious complications that can occur?
- What is a late complication of VZV post-transplant/immunocompromised?
1.
- Pneumonitis
- Encephalitis
- Hepatitis
- Purpura fulminans in neonate
- Acute retinal necrosis
- Progressive outer retinal necrosis
- VZV associated vasculopathy
- Shingles - VZV reactivation
- How can VZV infection be prevented?
- What is the treatment for VZV infection?
1.
- Aciclovir prophylaxis provides some protection
- Post-exposure prophylaxis of varicella with VZIg
2.
Aciclovir (first line)
Valaciclovir
What are the disease manifestations of CMV infection?
- Brain - encephalitis
- Eye - retinitis
- Lung - pneumonia
- Stomach and intestines - gastroenteritis
The transplant risk of CMV disease relates to what?
pre-tx serostatus
solid organ transplant:
- D+/R- : carries the greatest risk of reactivation
bone marrow transplant: adoptive immunity
- D-/R+ : carries the greatest risk of reactivation
What are the different options for CMV treatment and their main side effects
- Ganciclovir (IV): bone marrow suppression
- Valganciclovir: oral
- Foscarnet (IV) (nephrotoxicity)
- Cidofovir (nephrotoxicity)
- IVIg (with another drug for pneumonitis)
- What happens in the acute phase of an EBV infection?
- What happens after the acute phase?
- Acute phase: febrile illness with lymphadenopathy & moderate hepatitis
- After the acute phase: lifelong, latent, subclinical infection of B cells.
- Intermittent attempts at viral replication kept in check by immunosurveillance
- EBV stimulates host cells to divide – also kept in check.
- What is Post-transplant lymphoproliferative disease?
- What is the management of PTLD?
1.
- Associated with EBV
- Latently infected B cells – polyclonal activation
- Predisposes to lymphoma
- suspicion on rising EBV viral load (> 105 c/ml) and CT scan
- Confirmation with biopsy of lymph nodes
- Management:
- Reduce immunosuppression (regression in < 50%)
- Anti-CD20 monoclonal Ab therapy (B cell marker) (“rituximab”)
- How does Kaposi’s sarcoma present?
- What is it characterised by?
- How is it diagnosed?
- How is it treated?
- Which virus causes Kaposi’s sarcoma?
- Presents as a brownish/purplish vascular lesion, can be cutaneous or visceral
- Characterised by
- Spindle cell proliferation
- Neo-angiogenesis
- Inflammation and oedema
- Diagnosis made by biopsy
- Treated by chemotherapy and the initiation of antiretroviral therapy
- Caused by herpes virus - HHV-8
What type of virus is JC virus?
Polyomavirus
Which polyomavirus is associated with progressive multifocal leukoencephalopathy?
JC virus
- What is progressive multifocal leukoencephalopthy?
- What is the main pathological feature?
- How is it diagnosed?
- Cognitive disturbance, personality change, motor deficits other focal neurological signs
- The main pathological feature of PML is a demyelination of white matter with neurological deficits corresponding to the area(s) of the brain affected
- Diagnosis: MRI and PCR on CSF
- When is adenovirus a particular problem?
- What does it cause?
- Particular problem post-BMT - particularly in Paeds bone marrow transplant
2.
- Exogenous infection or reactivation of persistent endogenous infection.
- Fever
- Encephalitis/Pneumonitis/Colitis
A patient who received a stem cell transplant 2 weeks ago presents with mouth ulcers. Which of the following viral PCRs would you request on the mouth swab?
A. Enterovirus PCR
B. Adenovirus PCR
C. HSV PCR
D. HHV6 PCR
E. HHV8 PCR
C. HSV PCR
What virus causes progressive multifocal leukoencephalopathy?
JC virus
Which respiratory viruses are associated with high mortality and complications such as pneumonitis?
Increased risk of complications (pneumonitis) and high mortality associated particularly with:
- Influenza A and B
- Parainfluenza 1, 2, 3 and 4
- Respiratory Syncitial Virus (RSV) infection
- Adenovirus
- Novel coronavirus: MERS coronavirus
What is the treatment for Influenza A and B?
◦Oseltamivir (oral drug) for 5 days
If severely immunosupressed:
- risk of oseltamivir resistance
- zanamivir (inhalation or IV) is an alternative
- What can parvovirus B19 cause in the immunocompromised?
- How is it diagnosed?
- What is the treatment?
- Chronic anaemi
- Diagnosis:
- Serology (IgM) not useful in the immunocompromised
- PCR on blood
- Treatment:
Human normal immunoglobulin. May require blood transfusion
- What can happen to immunocompromised people with Hepatitis B infection?
- How can this be prevented?
- Two things can happen:
- Carriers may have flare of disease.
- Those who have had past infection can reactivate
- The risk of reactivation is particularly important with patients on B-cell depleting therapies (i.e Rituximab)
- Prevention:
* Nucleoside/nucleotide analogues (eg lamivudine, tenofovir, entecavir) prophylaxis
What are the main modes of transmission of Hepatitis E in developed countries?
- Through the consumption of undercooked meats such as pork
- Blood transfusion (less common)
- Possibly through organ donation
Please examine the following hepatitis B serology results, which profile is consistent with past hepatitis B infection?
(sag is surface antigen, sab is surface antibody)
A. HBV sag (+), HBV core ab (+), HBV sab (-)
B. HBV sag (-), HBV core ab (-), HBV sab>100mIU/ml
C. HBV sag (-), HBV core ab (-), HBV sab (-)
D. HBV sag (-), HBV core ab (+), HBV sab of 15mIU/ml
D. HBV sag (-), HBV core ab (+), HBV sab of 15mIU/ml
HBV sAg +
HBV core Ab + Current
HBV s Ab -
HBV s Ag -
HBV core Ab + Past
HBV s Ab +
HBV sAg -
HBV core Ab - Vaccination
HBV s Ab +
